The initiation and control of lymphocyte responses depend on the interaction of T cells with dendritic cells (DCs), a key type of antigen presenting cells (APCs). DCs are a complex innate immune cell population that recognize and respond to pathogen-associated and danger-associated signals. DCs are derived from bone-marrow progenitors and can be found in blood, lymphoid organs, and various tissues. Upon capture and process of pathogen-derived material, DCs present antigens in the context of MHC molecules on the surface of the cell. The interaction between TCR/co-receptor and MHC/peptide complex, and other co-stimulatory molecules presented on the surface of T cells and DCs, respectively, leads to activation and differentiation of naïve T cells.

Development

Mouse DC subsets

Human DC subsets

Myeloid cells in CNS

Maturation and Function

Products

Plasmacytoid DCs (pDCs) originate from myeloid (MDP) and lymphoid progenitors (LMPP) in bone marrow. This process includes sequential differentiation of MDP and LMPP to common dendritic cell precursors (CDP; mouse and human) and pre-pDC (mouse), respectively (1,2,5,6). The direct precursor of mouse and human classical/conventional DCs (cDCs), pre-cDC, is also derived from CDP. In comparison to pre-pDC, pre-cDCs undergo DC differentiation upon migration to tissues (3,4). In mice, several pre-cDC subsets have been identified (Siglec-H+Ly6C-, Siglec-H+Ly6C+, Siglec-H-Ly6C+, and Siglec-H-Ly6C-). Siglec-H and Ly6C serve as lineage markers that distinguish pre-cDC subpopulations committed to the cDC1 (Siglec-H-Ly6C- pre-DCs) or cDC2 lineages (Siglec-H-Ly6C+ pre-DCs)(1).

DC differentiation and maintenance strongly depends on the presence of FLT3L cytokine. In addition, cDC2 differentiation and CD11b+CD103- and CD11b-CD103- cell populations in the gut can be driven by monocytes in the presence of another cytokine, GM-CSF (7). In contrast, Langerhans cells are not derived from bone marrow progenitors. Instead, they differentiate early in ontogenesis from an embryonic cell progenitor present in the yolk sac (7).